The peptide therapy field experienced a transformative year in 2025, with researchers making significant strides in longevity science, metabolic health, and anti-aging interventions. The past year brought discoveries that range from mitochondrial therapeutics to AI-assisted peptide research which have the potential to reshape healthy aging and age-related disease treatment.
This roundup highlights the most impactful studies published in 2025, examining breakthroughs in peptide science that bring us closer to extending healthspan and improving metabolic function.
Highlights
- Mitochondrial peptides like humanin, MOTS-c, and elamipretide showed promise for cardiovascular aging, muscle function, and cellular energy metabolism
- Anti-aging vaccines targeting CD38 demonstrated the potential to reduce senescent cells and improve metabolic markers in animal models
- Marine and animal-derived peptides from cod collagen, velvet antler, and traditional sources exhibited lifespan extension and stress resistance benefits
- Artificial intelligence tools accelerated peptide discovery, while new oral delivery systems overcame traditional bioavailability barriers
Mitochondrial and Metabolic Peptides Lead the Way
Humanin and MOTS-c for Vascular Aging
Mitochondrial-derived peptides (MDPs) emerged as powerful regulators of cardiovascular aging in 2025. Research by Sivakumar and colleagues revealed that humanin and MOTS-c modulate apoptosis, inflammation, and oxidative stress through key pathways including AMPK, mTOR, and sirtuins.
These short peptides, encoded in mitochondrial DNA, show dual potential as both therapeutics and biomarkers for cardiovascular disease. The findings suggest MDPs could help predict vascular aging while offering targeted intervention strategies.
FGF21 Extends Lifespan Independent of Adiponectin
Fibroblast growth factor 21 (FGF21) demonstrated remarkable metabolic benefits in a 2025 study by Gliniak et al. In obese mice, FGF21 extended lifespan and improved insulin sensitivity even without adiponectin—a finding that challenges previous understanding of how this liver-derived peptide works.
The research highlights FGF21’s potential for treating metabolic syndrome and age-related diseases through pathways that operate independently of traditional metabolic signaling molecules.
GLP-1 Analogs Continue to Evolve
Proglucagon-derived peptides maintained their position at the forefront of metabolic research. Multiple studies examined next-generation GLP-1 receptor agonists and multi-receptor analogs, with research by Gasbjerg et al. and Król et al. mapping out broader applications beyond diabetes and obesity.
These peptides are being developed for gastrointestinal disorders, cardiovascular protection, and neuroprotection, demonstrating the versatility of the GLP-1 pathway in human physiology.
Anti-Aging Vaccines and Functional Peptide Therapeutics
CD38-Targeting Vaccine Shows Multi-System Benefits
One of the year’s most innovative approaches came from Yu et al., who developed a peptide vaccine targeting CD38—an enzyme that depletes cellular NAD+ levels during aging. The vaccine improved glucose tolerance, reduced senescent cell burden, and enhanced NAD+ metabolism in aged mice.
This immunological approach to slowing aging represents a shift from daily supplementation to long-lasting immune-mediated protection against age-related decline.
Elamipretide Improves Function Without Changing Molecular Age
Elamipretide, a mitochondria-targeted peptide, improved cardiac and skeletal muscle function in aged mice without detectably altering epigenetic or transcriptomic age markers, according to research by Mitchell and colleagues.
The study raises important questions about the relationship between functional improvement and molecular markers of aging. It suggests that peptide interventions can deliver meaningful health benefits even when traditional aging biomarkers remain unchanged.
Marine, Plant, and Animal-Derived Peptides Gain Traction
Collagen Peptides Extend Lifespan in Model Organisms
Two separate studies examined collagen-derived peptides from marine and traditional animal sources. Wei et al. demonstrated that cod collagen peptides extended lifespan and enhanced stress resistance in C. elegans, while Luo et al. showed similar benefits with Colla Corii Asini (donkey-hide gelatin) collagen peptides.
Both studies point to anti-senescence mechanisms and improved cellular stress responses as key drivers of the longevity benefits observed.
Velvet Antler Peptides for Neuroprotection
Research by Jiang and colleagues highlighted the neuroprotective, anti-oxidative, and immunomodulatory effects of velvet antler peptides. The review synthesized evidence supporting their use in delaying age-related neurological decline and supporting immune function during aging.
Plant Peptides Target Metabolic Liver Disease
Plant-derived bioactive peptides and protein hydrolysates showed promise for managing metabolic dysfunction-associated fatty liver disease (MAFLD). A systematic review by Santos-Sánchez and Cruz-Chamorro identified antioxidant and anti-inflammatory mechanisms that could make plant peptides valuable adjuncts to conventional MAFLD treatments.
Technological Breakthroughs Accelerate Discovery
AI-Powered Peptide Prediction
Datta and colleagues developed AAGP (Anti-Aging Peptide Predictor), a machine learning tool that integrates physicochemical and compositional features to identify anti-aging peptide candidates with high specificity. This computational approach dramatically reduces the time and cost associated with discovering new therapeutic peptides.
The tool represents a growing trend toward AI-assisted peptide design, which could accelerate the path from discovery to clinical application.
Oral Delivery Systems Overcome Traditional Barriers
Advances in oral delivery formulations addressed one of peptide therapy’s biggest challenges: bioavailability. Research by Jiao et al. and Rosson et al. demonstrated new approaches to protecting peptides from gastrointestinal degradation and improving absorption.
These innovations could expand patient access to peptide therapies by eliminating the need for injections, improving compliance and opening new markets for peptide-based treatments.
Comprehensive Datasets Enable Rational Design
New comprehensive peptide datasets published by Xiao et al. provide researchers with rich resources for understanding structure-function relationships. These multi-omics approaches facilitate the rational design of next-generation therapeutics by revealing how specific peptide sequences translate to biological activity.
Summary of Key 2025 Peptide Therapy Studies
| Study/Breakthrough | Key Findings | Therapeutic Focus | Citations |
|---|---|---|---|
| Mitochondrial-derived peptides (MDPs) | Regulate vascular aging, modulate AMPK/mTOR/sirtuins, potential biomarkers | Cardiovascular aging, longevity | Sivakumar et al., 2025 |
| FGF21 in obesity | Extends lifespan, improves insulin sensitivity, reduces inflammation | Metabolic syndrome, lifespan extension | Gliniak et al., 2025 |
| CD38-targeting peptide vaccine | Reduces senescence, improves metabolism, increases NAD+ | Anti-aging immunotherapy | Yu et al., 2025 |
| Elamipretide | Improves muscle/cardiac function, mitigates frailty | Sarcopenia, cardiac aging | Mitchell et al., 2025 |
| Marine/animal-derived peptides | Antioxidant, anti-aging, neuroprotective effects | Healthy aging, chronic disease prevention | Jiang et al., 2025; Wei et al., 2025; Liu et al., 2025; Guryanova & Ovchinnikova, 2025; Shahidi & Saeid, 2025 |
| AI-driven peptide discovery (AAGP) | Predicts anti-aging peptides with high specificity | Drug discovery, computational biology | Datta et al., 2025 |
| Oral peptide delivery advances | Overcomes GI barriers, improves compliance | Diabetes, obesity, metabolic diseases | Jiao et al., 2025; Rosson et al., 2025 |
| Proglucagon-derived peptide analogs | Multi-receptor agonists for metabolic/GI diseases | Diabetes, obesity, GI disorders | Gasbjerg et al., 2025; Król et al., 2025 |
Challenges and Future Directions
Stability and Translation Remain Key Hurdles
Despite remarkable progress, peptide stability, bioavailability, and long-term safety continue to challenge researchers. The transition from promising animal studies to effective human therapies requires robust clinical trials and standardized methodologies.
Precision Medicine on the Horizon
The field is moving toward biomarker-guided interventions and combination therapies. Research by Cordos et al., Chen et al., and Tan et al. explored synergistic approaches that combine peptide therapies with autophagy activators, senolytics, and metabolic regulators.
This precision approach—matching specific peptides to individual patient profiles based on biomarkers—may define the next era of longevity medicine.
What 2025’s Research Signals for the Future
The studies published in 2025 demonstrate that peptide therapeutics have matured beyond single-target interventions to become sophisticated tools for addressing the complex biology of aging and metabolic disease.
From mitochondrial function to immune-mediated anti-aging strategies, from marine-derived compounds to AI-discovered sequences, the field is expanding in both breadth and depth. As delivery technologies improve and our understanding of aging mechanisms grows more nuanced, peptide therapies are positioned to play a central role in extending human healthspan.
The momentum gained in 2025 sets the stage for even greater advances as science, technology, and clinical practice converge around the goal of healthy longevity.
Medical Disclaimer: This article is for educational purposes only and is not intended as medical advice. All peptide therapies discussed are under investigation and may not be approved for human use. Consult qualified healthcare professionals before considering any therapeutic interventions.
References
Chen, J., Leung, G., Leung, H., Ustiugova, A., Shneyderman, A., Korzinkin, M., Gennert, D., Pun, F., Aliper, A., Ren, F., & Zhavoronkov, A. (2025). From clock to clock: Therapeutic target discovery for aging and age-related diseases. Ageing Research Reviews, 112. https://doi.org/10.1016/j.arr.2025.102871
Cordos, B., Tero-Vescan, A., Hampson, I., Oliver, A., & Slevin, M. (2025). Synergistic Autophagy-Related Mechanisms of Protection Against Brain Aging and AD: Cellular Pathways and Therapeutic Strategies. Pharmaceuticals, 18. https://doi.org/10.3390/ph18060829
Datta, S., Yu, J., Lin, Y., Cheng, Y., & Chen, C. (2025). AAGP integrates physicochemical and compositional features for machine learning-based prediction of anti-aging peptides. Scientific Reports, 15. https://doi.org/10.1038/s41598-025-12759-0
Gasbjerg, L., Nielsen, C., Suppli, M., Grøendahl, M., Holst, J., Knop, F., Jeppesen, P., & Lund, A. (2025). Proglucagon-derived Peptides: Human Physiology and Therapeutic Potential. Physiological Reviews. https://doi.org/10.1152/physrev.00057.2024
Gliniak, C., Gordillo, R., Youm, Y., Lin, Q., Crewe, C., Zhang, Z., Field, B., Fujikawa, T., Virostek, M., Zhao, S., Zhu, Y., Rosen, C., Horvath, T., Dixit, V., & Scherer, P. (2025). FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression. Cell Metabolism. https://doi.org/10.1016/j.cmet.2025.05.011
Guryanova, S., & Ovchinnikova, T. (2025). Multifaceted Marine Peptides and Their Therapeutic Potential. Marine Drugs, 23. https://doi.org/10.3390/md23070288
Haoxin, H., Pei, H., Geng, J., Chen, W., Zong, Y., Zhao, Y., Du, R., & He, Z. (2025). Efficacy of velvet antler peptides in anti-aging: a narrative review. Aging Advances. https://doi.org/10.4103/agingadv.agingadv-d-24-00029
Jiang, Y., Zheng, J., Zhang, Y., Liu, Y., Zeng, L., & Han, W. (2025). Discovery of Deer Antler-Derived Antioxidant Peptides Through Computational and Cell-Based Approaches. Antioxidants (Basel, Switzerland), 14(10), 1169. https://doi.org/10.3390/antiox14101169
Jiao, Q., Huang, Y., He, J., & Xu, Y. (2025). Advances in Oral Biomacromolecule Therapies for Metabolic Diseases. Pharmaceutics, 17. https://doi.org/10.3390/pharmaceutics17020238
Król, M., Kupnicka, P., Żychowska, J., Kapczuk, P., Szućko-Kociuba, I., Prajwos, E., & Chlubek, D. (2025). Molecular Insights into the Potential Cardiometabolic Effects of GLP-1 Receptor Analogs and DPP-4 Inhibitors. International Journal of Molecular Sciences, 26. https://doi.org/10.3390/ijms26146777
Liu, T., Song, X., Dai, X., Haoxin, H., Muhammad, A., He, Z., & Zhao, K. (2025). Effects of animal-derived peptides on aging-related diseases: a narrative review. Aging Advances. https://doi.org/10.4103/agingadv.agingadv-d-25-00012
Luo, Q., Zhang, S., Sun, Z., Wang, Z., Yue, Q., Sun, X., Tian, L., Li, B., Li, K., Zhao, C., Zhao, L., & Su, L. (2025). Protective effects of Colla Corii Asini Collagen Peptides on D-galactose injection combined with UVB irradiation-induced aging in mice. PLOS ONE, 20. https://doi.org/10.1371/journal.pone.0317302
Mitchell, W., Pharaoh, G., Tyshkovskiy, A., Campbell, M., Marcinek, D., & Gladyshev, V. (2025). The Mitochondria-Targeted Peptide Therapeutic Elamipretide Improves Cardiac and Skeletal Muscle Function During Aging Without Detectable Changes in Tissue Epigenetic or Transcriptomic Age. Aging Cell, 24. https://doi.org/10.1111/acel.70026
Rosson, E., Lux, F., David, L., Godfrin, Y., Tillement, O., & Thomas, E. (2025). Focus on therapeutic peptides and their delivery. International Journal of Pharmaceutics, 125555. https://doi.org/10.1016/j.ijpharm.2025.125555
Santos-Sánchez, G., & Cruz-Chamorro, I. (2025). Plant-derived bioactive peptides and protein hydrolysates for managing MAFLD: A systematic review of in vivo effects. Food Chemistry, 481, 143956. https://doi.org/10.1016/j.foodchem.2025.143956
Shahidi, F., & Saeid, A. (2025). Bioactivity of Marine-Derived Peptides and Proteins: A Review. Marine Drugs, 23. https://doi.org/10.3390/md23040157
Sivakumar, R., Senghor, K., Vinodhini, V., & Kumar, J. (2025). Mitochondrial-Derived Peptides as Therapeutics and Biomarkers for Combating Vascular Aging and Associated Cardiovascular Diseases. Current Cardiology Reviews. https://doi.org/10.2174/011573403×375709250616134726
Tan, E., Lyang, N., Doroodian, S., Sanz-Martinez, P., Xu, J., Zaretski, S., Nieto-Torres, J., Ebata, H., Lim, S., Hou, W., Clay, K., Yoon, L., Massey, L., Rhoades, D., Garza, D., Johnson, K., To, A., Ambaye, L., Bentley, E., Petrascheck, M., Stolz, A., Kelly, J., & Hansen, M. (2025). Autophagy activator AA-20 improves proteostasis and extends Caenorhabditis elegans lifespan. Proceedings of the National Academy of Sciences of the United States of America, 122 (32), e2423455122. https://doi.org/10.1073/pnas.2423455122
Wei, J., Zhang, J., Ding, N., Liu, Y., Wu, Y., & Duan, R. (2025). Anti-Aging Effects and Mechanisms of Cod Collagen Peptides (CCPs) in Caenorhabditis elegans. Journal of Functional Biomaterials, 16. https://doi.org/10.3390/jfb16050150
Xiao, B., Zhou, Y., Zhao, L., Huang, H., Fei, X., & Zhang, Y. (2025). A comprehensive dataset of therapeutic peptides on multi-function property and structure information. Scientific Data, 12. https://doi.org/10.1038/s41597-025-05528-1
Yu, S., Li, Z., Tang, Y., Chen, Y., Y., Y., Du, K., Zong, Z., Feng, K., Wei, Y., Chen, L., & Deng, H. (2025). CD38-Targeting Peptide Vaccine Ameliorates Aging-Associated Phenotypes in Mice. Aging Cell, e70147. https://doi.org/10.1111/acel.70147
Zakir, S., Jawed, B., Esposito, J., Kanwal, R., Pulcini, R., Martinotti, R., Ceci, E., Botteghi, M., Gaudio, F., Toniato, E., & Martinotti, S. (2025). The Role of Peptides in Nutrition: Insights into Metabolic, Musculoskeletal, and Behavioral Health: A Systematic Review. International Journal of Molecular Sciences, 26. https://doi.org/10.3390/ijms26136043
Zhang, Z., & Svensson, K. (2025). Discovery of peptides as key regulators of metabolic and cardiovascular crosstalk. Cell Reports, 44, 115836 – 115836. https://doi.org/10.1016/j.celrep.2025.115836
